Biomedical subjects

Alvaro A Martinez

Publications and source records attributed to Alvaro A Martinez.

At least 37 records · Page 2Linked to original sources

PubMed2005

Cone-beam-CT guided radiation therapy: technical implementation.

BACKGROUND AND PURPOSE: X-ray volumetric imaging system (XVI) mounted on a linear accelerator is available for image guidance applications. In preparation for clinical implementation, phantom and patient imaging studies were conducted to determine the irradiation parameters that would trade-off image quality, patient dose and scanning time. PATIENTS AND METHODS: The XVI image quality and imaging dose were benchmarked against those obtained with a helical CT scanner for a head and body phantom. The irradiation parameters were varied including the total imaging dose, number of projections, field of view, reconstruction resolution and use of a scatter rejection grid. We characterized the image quality based on relative contrast, noise, contrast to noise ratio (CNR) and point spread function (PSF). XVI scans of pelvis, head and neck and lung patients were acquired and submitted to a range of observers to identify the favorable reconstruction parameters. RESULTS: Phantom studies have demonstrated that a scatter rejection grid reduces photon scattering and improves the image uniformity. For the body phantom, the helical CT and the wide field XVI technique produce similar image quality, with surface doses of 0.025 and 0.044 Gy respectively. We have demonstrated that the local tomography technique improves the image contrast and the CNR while reducing the skin dose by 40-50% compared to the wide field technique. Clinical scans of head and neck, lung and prostate patients present good soft tissue contrast and excellent bone definition. CONCLUSIONS: With adjustment of irradiation parameters and an imaging surface dose of less than 0.05 Gy, high quality XVI images can be obtained for a phantom simulating the body thickness. XVI is currently feasible for image-guided treatments of head and neck, torso and pelvic areas using soft tissue and bony structures.

Humans↗

PubMed2005

Vaginal brachytherapy alone: an alternative to adjuvant whole pelvis radiation for early stage endometrial cancer.

OBJECTIVE: Postoperative management of early stage adenocarcinoma of the endometrium remains controversial. The use of pelvic radiation therapy as shown by the Gynecologic Oncology Group (GOG)-99 trial improves the event free interval at the cost of increased toxicity. We reviewed and compared our results treating early stage endometrial adenocarcinoma using hypofractionated high dose rate (HDR) vaginal brachytherapy (VB) alone with the results of the GOG-99. METHODS: From 1992 to 2002, 243 endometrial cancer patients were treated with TAH/BSO and selective lymph node dissection followed by adjuvant radiotherapy (RT). Of these, 50 FIGO stage I-II (occult) adenocarcinoma (no clear cell or serous papillary) of the endometrium were managed with HDR hypofractionated VB as monotherapy using Iridium-192 to a dose of 30 Gy in 6 fractions twice weekly prescribed to a depth of 5 mm and median length of 4 cm. The characteristics, toxicity rates, and outcomes of our patients were compared with the results of the GOG-99. The median follow up of our patients and the GOG-99 were 3.2 years and 5.8 years, respectively. RESULTS: Patient characteristics including age, stage, and grade were similar in our study and the GOG-99. The local recurrence rate in our study, the pelvic RT arm of the GOG-99, and the no RT arm of the GOG-99 were 4% (n = 2), 2% (n = 3), and 9% (n = 18), respectively. In our study, one patient failed in the vagina alone and a second patient failed in the vagina and pelvis. In the GOG-99, the vagina as a component of locoregional failure was also the most common failure site in the no RT arm 77.8% (n = 14) and in the RT arm 100% (n = 3). The 2-year cumulative recurrence rate in our study was 2%, which compares favorably with the GOG-99 pelvic RT arm (3%) and observation arm (12%). Four-year survival rates of the no RT arm of the GOG-99, the RT arm of the GOG-99, and our study with HDR VB were 86%, 92%, and 97%, respectively. Chronic grade 2 toxicity rates were reduced by the use of VB compared to pelvic RT, especially GI toxicity 0% vs. 34% (P value < 0.001), and GI obstruction 0% vs. 7% (P value = 0.08). CONCLUSION: Stage I-II (occult) endometrial adenocarcinoma treated with postoperative HDR vaginal brachytherapy has similar overall survival, locoregional failure rates, and cumulative recurrence rates to standard fractionation external beam pelvic RT with the benefit of much lower toxicity rates and shorter overall treatment time.

Adenocarcinoma↗

PubMed2005

Definitions of biochemical failure that best predict clinical failure in patients with prostate cancer treated with external beam radiation alone: a multi-institutional pooled analysis.

PURPOSE: Pooled data on 4,839 patients with T1-2 prostate cancer treated with external beam radiation therapy (RT) alone at 9 institutions have previously provided long-term biochemical failure (BF) and clinical outcomes using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition. In this report we determined the sensitivity and specificity of several BF definitions using distant failure (DF) alone or clinical failure (CF), defined as local failure (LF) and/or DF. MATERIALS AND METHODS: The pooled cohort was treated between 1986 and 1995 with external beam RT (60 Gy or greater) without pre-RT androgen suppression or planned post-RT adjuvant androgen suppression. Median followup was 6.3 years. The sensitivity and specificity of 102 definitions of BF relative to DF and LF were assessed. RESULTS: The BF definitions with higher sensitivity and specificity than the ASTRO definition for DF only and CF are reported. The sensitivity and specificity of the ASTRO definition to predict DF alone was 55% and 68%, respectively. Three definitions had higher sensitivity and specificity, namely prostate specific antigen (PSA) greater than current nadir (lowest PSA prior to current measurement) plus 3 ng/ml (sensitivity 76% and specificity 72%), dated at the call (failure date as the date when the criterion was met), PSA greater than absolute nadir plus 2 ng/ml (sensitivity 72% and specificity 70%), dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated (sensitivity 69% and specificity 73%). The sensitivity and specificity of the ASTRO definition to predict CF was 60% and 72%, respectively. Three definitions had higher sensitivity and specificity, namely PSA greater than current nadir plus 3 ng/ml (sensitivity 66% and specificity 77%), dated at the call, PSA greater than absolute nadir plus 2 ng/ml (sensitivity 64% and specificity 74%), dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated (sensitivity 67% and specificity 78%). CONCLUSIONS: Using what is to our knowledge the largest data set of patients with prostate cancer treated with RT alone we correlated multiple definitions of BF with the strict clinical end points of DF alone and CF (DF or local failure). Defining BF as PSA greater than absolute nadir plus 2 ng/ml, dated at the call, PSA greater than current nadir plus 3 ng/ml, dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated, had higher sensitivity and specificity for DF alone or CF compared with the ASTRO definition. This information should contribute to the discussion regarding suggested modifications to the ASTRO definition of biochemical failure.

Adult↗

PubMed2004

Defining a radiotherapy target with positron emission tomography.

PURPOSE: F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is now considered the most accurate clinical staging study for non-small-cell lung cancer (NSCLC) and is also important in the staging of multiple other malignancies. Gross tumor volume (GTV) definition for radiotherapy, however, is typically based entirely on computed tomographic data. We performed a series of phantom studies to determine an accurate and uniformly applicable method for defining a GTV with FDG-PET. METHODS AND MATERIALS: A model-based method was tested by a phantom study to determine a threshold, or unique cutoff of standardized uptake value based on body weight (standardized uptake value [SUV]) for FDG-PET based GTV definition. The degree to which mean target SUV, background FDG concentration, and target volume influenced that GTV definition were evaluated. A phantom was constructed consisting of a 9.0-L cylindrical tank. Glass spheres with volumes ranging from 12.2 to 291.0 cc were suspended within the tank, with a minimum separation of 4 cm between the edges of the spheres. The sphere volumes were selected based on the range of NSCLC patient tumor volumes seen in our clinic. The tank and spheres were filled with a variety of known concentrations of FDG in several experiments and then scanned using a General Electric Advance PET scanner. In the initial experiment, six spheres with identical volumes were filled with varying concentrations of FDG (mean SUV = 1.85 approximately 9.68) and suspended within a background bath of FDG at a similar concentration to that used in clinical practice (0.144 muCi/mL). The second experiment was identical to the first, but was performed at 0.144 and 0.036 muCi/mL background concentrations to determine the effect of background FDG concentration on sphere definition. In the third experiment, six spheres with volumes of 12.2 to 291.0 cc were filled with equal concentrations of FDG and suspended in a standard background FDG concentration of 0.144 muCi/mL. Sphere images in each experiment were auto-contoured (simulating a GTV) using the threshold SUV that yielded a volume matching that of the known sphere volume. A regressive function was constructed to represent the relationship between the threshold SUV and the mean target SUV. This function was then applied to define the GTV of 15 NSCLC patients. The GTV volumes were compared to those determined by a fixed image intensity threshold proposed by other investigators. RESULTS: There was a strong linear relationship between the threshold SUV and the mean target SUV. The linear regressive function derived was: threshold SUV = 0.307 x (mean target SUV) + 0.588. The background concentration and target volume indirectly affect the threshold SUV by way of their influence on the mean target SUV. We applied the linear regressive function, as well as a fixed image intensity threshold (42% of maximum intensity) to the sphere phantoms and 15 patients with NSCLC. The results indicated that a much smaller deviation occurred when the threshold SUV regressive function was utilized to estimate the phantom volume as compared to the fixed image intensity threshold. The average absolute difference between the two methods was 21% with respect to the true phantom volume. The deviation became even more pronounced when applied to true patient GTV volumes, with a mean difference between the two methods of 67%. This was largely due to a greater degree of heterogeneity in the SUV of tumors over phantoms. CONCLUSIONS: An FDG-PET-based GTV can be systematically defined using a threshold SUV according to the regressive function described above. The threshold SUV for defining the target is strongly dependent on the mean target SUV of the target, and can be uniquely determined through the proposed iteration process.

Body Weight↗

PubMed2004

Changes in temporal patterns of local failure after breast-conserving therapy and their prognostic implications.

PURPOSE: The purpose of this analysis was to evaluate patterns and rates of ipsilateral breast tumor recurrence (IBTR) over time based on the type of failure (true recurrence/marginal miss [TR/MM] vs. elsewhere [E]) and to compare these to rates of contralateral failure in women with Stages I/II breast cancer treated with conservative surgery (CS) and radiation therapy (RT). METHODS AND MATERIALS: Between 1980 and 1997, 1448 patients with Stages I/II invasive breast carcinoma were treated with CS and RT to a median total dose of >60 Gy. IBTRs were analyzed in terms of their location as follows: TR/MM, referring to those occurring in the same quadrant, and E, referring to the development of a malignancy remote from the index lesion. Outcomes were characterized in terms of their temporal recurrence patterns and correlated with rates of contralateral breast failure (CL). The median follow-up was 8.5 years. RESULTS: A total of 79 ipsilateral and 98 contralateral failures were observed during the follow-up period corresponding to 5-, 10-, and 15-year actuarial rates of 2%, 7%, and 10% and 4%, 9%, and 12% respectively. Fifty-nine ipsilateral failures (74.7%) were designated as TR/MM and 20 (25.3%) as E. The corresponding 5-, 10-, and 15-year actuarial rates of TR/MM and E failures were 2%, 5%, and 8% and 0.1%, 2%, and 3%, respectively. The median times to total ipsilateral, TR/MM, E, and contralateral failure were 6.5, 5.7, 7.4, and 5.2 years, respectively. Between 0 and 5 years of follow-up, E failures represented 7% of the total ipsilateral failures observed. From 5-10 and 10-15 years, E failures represented 39% and 27% of the total, respectively (p = 0.01). Contralateral failure was significantly more likely to occur in the first 5 years of follow-up than IBTR, accounting for 50 (63.3%) of the 79 failures in that interval (p = 0.02). No significant differences in survival rates were detected between any of the various failure types. On multivariate analysis, only reduced time to tumor recurrence was found to be adversely associated with overall survival. CONCLUSIONS: The rates and patterns of IBTR vary with time and, after 5 years, approach the rates of development of a contralateral breast cancer. E failures are, overall, less frequent than TR/MM but contribute increasingly to the IBTR rate after 5 years. Time to tumor recurrence is the most reliable predictor of prognosis after IBTR.

Adult↗

PubMed2004

The validity of surgical clips as a radiographic surrogate for the lumpectomy cavity in image-guided accelerated partial breast irradiation.

PURPOSE: We hypothesize that surgical clips placed in the biopsy cavity during lumpectomy can be used as radiographic markers to facilitate image-guided external beam accelerated partial breast irradiation. METHODS AND MATERIALS: We evaluated 28 patients with surgically placed clips in the lumpectomy cavity and two CT scans on different days. To establish whether the clips remain predictive of the lumpectomy cavity throughout therapy, we analyzed the motion of both cavities with repeat volumetric CT scans. The three-dimensional (3D) locations of each lumpectomy cavity and the associated clips were defined as individual regions of interest (ROIs). A single point of interest (POI) was defined for each ROI. The calculated movements of the lumpectomy cavity POIs between different scans were compared to those of the clip POIs. The second CT data set was then moved in accordance to the calculated clip POI's movement. The volume of the (second) lumpectomy cavity associated with the second scan outside of the (first) cavity of the first scan was measured. In addition, the required amount of a radial margin expansion around the first lumpectomy cavity to ensure coverage of the second lumpectomy cavity both before and after moving the second lumpectomy according to the clip POI movement was calculated. RESULTS: The two CT scans were obtained on average 27 days apart, and the mean lumpectomy size decreased from 35 to 16 cc. The clip and lumpectomy cavity POIs moved a mean of 3 mm along the three principal Cartesian axes. In moving the second lumpectomy cavity according to the clip POI displacement from its original position, the volume of the second lumpectomy cavity outside of the volume of the first decreased from 2.6 cc to 1.0 cc after correction, and the required radial margin on the first lumpectomy cavity to include the second lumpectomy cavity decreased from 5.5 mm vs. 3.8 mm. CONCLUSION: The surgically placed clips after lumpectomy are strong radiographic surrogates for the biopsy cavity. If the clips were used to guide accelerated partial breast irradiation, a planning target volume margin of the order of 5 mm could be used, significantly smaller than the 10-mm margin currently employed.

Breast Neoplasms↗

PubMed2004

Potential survival advantage with early androgen deprivation for biochemical failure after external beam radiotherapy: the importance of accurately defining biochemical disease status.

PURPOSE: We analyzed our experience treating localized prostate cancer to determine the impact of androgen deprivation (AD) on clinical outcome if administered at the time of isolated biochemical failure (BF) vs. after clinical failure (clinical failure), and the associated impact of various BF definitions. METHODS: A total of 1,201 patients with stage T1-T3N0M0 prostate cancer were treated with external beam radiotherapy (EBRT) to a median dose of 66.6 Gy. Early AD was defined as administration of AD after BF, without evidence of clinical failure. Delayed AD was defined as administration of AD after clinical failure. Multiple BF definitions were tested for capacity to predict subsequent clinical failure. For each BF definition, outcome was compared for BF patients receiving early AD vs. no or delayed AD. RESULTS: Five-year clinical failure (from date of BF) was 60% for patients who experienced a prostate-specific antigen rise to >/=3 ng/mL above nadir. For these patients, early AD was associated with decreased 5-year local failure (4% vs. 33%), distant metastasis (13% vs. 44%), cause-specific death (9% vs. 24%), and death due to any cause (32% vs. 48%), despite poorer prognostic factors in patients receiving early AD. On multivariate analysis, early AD remained independently significant for each of these end points. CONCLUSION: The efficacy of AD after BF varies depending on the BF definition. When an optimal BF definition is applied, early AD decreases distant metastasis and improves survival. Prostate-specific antigen elevation to >/=2 or >/=3 ng/mL above nadir seems optimal in establishing clinically significant BF and the timing of AD intervention.

Adult↗

PubMed2004

Impact of breathing motion on whole breast radiotherapy: a dosimetric analysis using active breathing control.

PURPOSE: The active breathing control (ABC) apparatus was used to quantify the effect of breathing motion on whole breast radiotherapy (RT) with standard wedges and intensity-modulated RT (IMRT). METHODS AND MATERIALS: Ten patients with early-stage breast cancer underwent routine free-breathing (FB) CT simulations for whole breast RT. An ABC apparatus was used to obtain two additional CT scans with the breath held at the end of normal inhalation and normal exhalation. The FB scan was used to develop both a standard treatment plan using wedged coplanar tangents and an IMRT plan using multiple static multileaf collimator segments. To simulate breathing, each plan was copied and applied to the normal inhalation and normal exhalation CT scans. RESULTS: The medial field border (defined by a radiopaque catheter) for the normal inhalation and normal exhalation scans moved an average of 0.6 cm anteriorly and 0.3 cm posteriorly compared with the FB position, respectively. The corresponding movement of the lateral field border was an average of 0.4 cm anteriorly and 0.2 cm posteriorly compared with the FB position. For both the wedged and the IMRT techniques, the dose delivered to breast tissue, biopsy cavity, and ipsilateral lung was similar for each of the three CT scan positions. However, the internal mammary node dose varied significantly with breathing. CONCLUSIONS: The dose delivered to breast using standard wedges or step-and-shoot IMRT is relatively insensitive to the effects of breast motion during normal breathing. However, an appreciable portion of the internal mammary nodes are irradiated during normal inhalation, contributing to the uncertainty in the analysis of the efficacy of internal mammary nodal RT in breast treatment.

Breast Neoplasms↗

PubMed2004

High dose rate brachytherapy as prostate cancer monotherapy reduces toxicity compared to low dose rate palladium seeds.

PURPOSE: We evaluated the potential for differing acute and chronic toxicities between 2 monotherapy methods of image guided conformal brachytherapy, high dose rate (HDR) brachytherapy alone and low dose rate (LDR) permanent palladium seeds. MATERIALS AND METHODS: A total of 149 patients with biopsy proven, early stage prostate cancer were consecutively treated with interstitial brachytherapy as the sole method of treatment at William Beaumont Hospital between 1999 and 2001. Of the 149, 65 patients were treated with HDR using 192 iridium (192Ir), and 84 patients were treated with LDR using 103 palladium (103Pd). The majority of patients had clinical stage II, T1c or T2a disease, pretreatment prostate specific antigen less than 10 ng/ml and Gleason score 6 or less. Neoadjuvant hormones were used in 36% of patients for gland volume optimization. All treatments were performed transperineally with trans-rectal ultrasound guidance and fluoroscopy for verification of needle/seed positions. The HDR dose was 38 Gy delivered in 4 fractions, 2 times daily during 2 days. The LDR dose was 120 Gy. Acute and chronic toxicities were scored according to the Common Toxicity Criteria scale, version 2.0. RESULTS: Median followup for all patients was 35 months. The 2 treatment groups were well-balanced with respect to age, clinical stage, prostate specific antigen, Gleason score, use of neoadjuvant hormones, pretreatment genitourinary symptoms, implanted gland volume and length of followup. Biochemical control (American Society for Therapeutic Radiology and Oncology definition) was 97% and 98% for LDR and HDR, respectively. HDR brachytherapy alone was associated with decreased acute rates of grade 1 to 3 dysuria (67% versus 36%, p <0.001), urinary frequency/urgency (92% versus 54%, p <0.001) and rectal pain (20% versus 6%, p = 0.017). These differences remained significant when patients who received prior hormonal therapy were excluded from analysis. Selected chronic toxicities were also decreased with HDR, including long-term urinary frequency and urgency, 32% (HDR) vs 56% (103Pd), p = 0.004. There were no differences in the rates of chronic dysuria, urinary incontinence, retention or hematuria. Urethral stricture rates were 8% in the HDR alone group vs 3% for 103 Pd (p = 0.177). The 3-year actuarial impotence rate was 45% for the LDR group and only 16% for HDR. The majority of complications were grade 1. No grade 4 toxicities were encountered in either group. HDR decreased treatment cost by 19%. CONCLUSIONS: While HDR (192 iridium) and LDR (103Pd) monotherapy maintained the same biochemical control, the use of HDR brachytherapy as monotherapy was associated with decreased rates of acute urinary frequency, urgency, dysuria and rectal pain compared to LDR. Chronic urinary frequency, urgency and grade 2 rectal toxicities were also decreased with HDR. A dramatic decrease (66%) was noted in the rate of sexual impotency with HDR. In addition, patients treated with HDR did not remain radioactive after treatment. There was a decrease in cost from not purchasing seeds per patient. HDR monotherapy as prostate cancer treatment resulted in the same biochemical control with much lower toxicity. It is an accepted, convenient, cost-effective method of prostate brachytherapy for patients with favorable risk prostate cancer.

Adenocarcinoma↗

PubMed2003

Long-term multi-institutional analysis of stage T1-T2 prostate cancer treated with radiotherapy in the PSA era.

PURPOSE: To report the long-term outcome for patients with Stage T1-T2 adenocarcinoma of the prostate definitively irradiated in the prostate-specific antigen (PSA) era. METHODS AND MATERIALS: Nine institutions combined data on 4839 patients with Stage T1b, T1c, and T2 adenocarcinoma of the prostate who had a pretreatment PSA level and had received >or=60 Gy as definitive external beam radiotherapy. No patient had hormonal therapy before treatment failure. The median follow-up was 6.3 years. The end point for outcome analysis was PSA disease-free survival at 5 and 8 years after therapy using the American Society for Therapeutic Radiology and Oncology (ASTRO) failure definition. RESULTS: The PSA disease-free survival rate for the entire group of patients was 59% at 5 years and 53% at 8 years after treatment. For patients who had received >or=70 Gy, these percentages were 61% and 55%. Of the 4839 patients, 1582 had failure by the PSA criteria, 416 had local failure, and 329 had distant failure. The greatest risk of failure was at 1.5-3.5 years after treatment. The failure rate was 3.5-4.5% annually after 5 years, except in patients with Gleason score 8-10 tumors for whom it was 6%. In multivariate analysis for biochemical failure, pretreatment PSA, Gleason score, radiation dose, tumor stage, and treatment year were all significant prognostic factors. The length of follow-up and the effect of backdating as required by the ASTRO failure definition also significantly affected the outcome results. Dose effects were most significant in the intermediate-risk group and to a lesser degree in the high-risk group. No dose effect was seen at 70 or 72 Gy in the low-risk group. CONCLUSION: As follow-up lengthens and outcome data accumulate in the PSA era, we continue to evaluate the efficacy and durability of radiotherapy as definitive therapy for early-stage prostate cancer. Similar studies with higher doses and more contemporary techniques will be necessary to explore more fully the potential of this therapeutic modality.

Adenocarcinoma↗

PubMed2003

Three-dimensional evaluation of intra- and interfraction immobilization of lung and chest wall using active breathing control: a reproducibility study with breast cancer patients.

PURPOSE: A CT-based three-dimensional (3D) method was used to analyze the intra- and interfraction reproducibility of lung immobilization during moderate deep inspiration breath hold (mDIBH), defined as 75% of the maximal inspiration using an active breathing control (ABC) apparatus. METHODS AND MATERIALS: The ABC apparatus was used to immobilize the breathing motion with a computer-controlled valve. Immobilization of the lungs in breast cancer patients was used as a model to evaluate the reproducibility of mDIBH using the ABC apparatus. CT scans were acquired twice at mDIBH in the same session for 30 breast cancer patients. Twenty-three of them were immobilized with an alpha-cradle, of which 14 had a repeat scan at mDIBH 1-4 weeks later. Twelve of those patients received intensity-modulated radiotherapy to the left breast at mDIBH to displace the heart from the beam. The remaining patients were treated at free breathing, with either intensity-modulated irradiation to the whole breast or conformal partial breast irradiation. To remove the component of setup error, mDIBH scans were registered with respect to the vertebrae. The lungs and carina were auto-contoured to form 3D surfaces for each data set. The closest distance-to-agreement (DTA) for each point between the 3D surfaces of the corresponding CT scans was displayed on a 3D surface map. For analysis, each lung was divided along its inferior to superior extent into six regions, from the basal 10%, the next four consecutive 20% sections in height, to the last apical 10%. Likewise, the carina was divided into regions of the trachea and bifurcation. The mean and standard deviation (SD) of the DTA for each of these regions was computed. RESULTS: With the patient positioned in an alpha-cradle, the mean +/- SD intrafraction DTA was 1.5 +/- 1.4 mm for the left lung and 1.0 +/- 1.4 mm for the right lung. The corresponding values without the use of an alpha-cradle were significantly greater, with 1.9 +/- 2.1 mm and 2.2 +/- 2.2 mm for the left and right lung, respectively (p <0.005 for the SD of the left lung and p <0.0003 for the SD of the right lung). The interfraction DTA for the left and right lungs was 1.4 +/- 1.7 mm and 1.4 +/- 1.6 mm, respectively. The regional analysis demonstrated better immobilization for the upper two-thirds of the chest wall compared with that for the lung base. The DTA values obtained for the tracheal bifurcation were 0.9 +/- 0.8 mm for intrafraction and 1.4 +/- 1.0 mm for interfraction. CONCLUSION: The ABC device can be used to reduce respiratory motion at mDIBH in breast cancer patients or those patients who can perform the maneuver. This device demonstrated excellent intra- and interfraction reproducibility of chest wall and carina immobilization, especially when combined with alpha-cradle immobilization. Internal margins for suspended breathing can be extrapolated from these data for various anatomic regions within the lung and chest wall.

Breast Neoplasms↗

PubMed2003

Potential for reduced toxicity and dose escalation in the treatment of inoperable non-small-cell lung cancer: a comparison of intensity-modulated radiation therapy (IMRT), 3D conformal radiation, and elective nodal irradiation.

PURPOSE: To systematically evaluate four different techniques of radiation therapy (RT) used to treat non-small-cell lung cancer and to determine their efficacy in meeting multiple normal-tissue constraints while maximizing tumor coverage and achieving dose escalation. METHODS AND MATERIALS: Treatment planning was performed for 18 patients with Stage I to IIIB inoperable non-small-cell lung cancer using four different RT techniques to treat the primary lung tumor +/- the hilar/mediastinal lymph nodes: (1) Intensity-modulated radiation therapy (IMRT), (2) Optimized three-dimensional conformal RT (3D-CRT) using multiple beam angles, (3) Limited 3D-CRT using only 2 to 3 beams, and (4) Traditional RT using elective nodal irradiation (ENI) to treat the mediastinum. All patients underwent virtual simulation, including a CT scan and (18)fluorodeoxyglucose positron emission tomography scan, fused to the CT to create a composite tumor volume. For IMRT and 3D-CRT, the target included the primary tumor and regional nodes either > or =1.0 cm in short-axis dimension on CT or with increased uptake on PET. For ENI, the target included the primary tumor plus the ipsilateral hilum and mediastinum from the inferior head of the clavicle to at least 5.0 cm below the carina. The goal was to deliver 70 Gy to > or =99% of the planning target volume (PTV) in 35 daily fractions (46 Gy to electively treated mediastinum) while meeting multiple normal-tissue dose constraints. Heterogeneity correction was applied to all dose calculations (maximum allowable heterogeneity within PTV 30%). Pulmonary and esophageal constraints were as follows: lung V(20) < or =25%, mean lung dose < or =15 Gy, esophagus V(50) < or =25%, mean esophageal dose < or =25 Gy. At the completion of all planning, the four techniques were contrasted for their ability to achieve the set dose constraints and deliver tumoricidal RT doses. RESULTS: Requiring a minimum dose of 70 Gy within the PTV, we found that IMRT was associated with a greater degree of heterogeneity within the target and, correspondingly, higher mean doses and tumor control probabilities (TCPs), 7%-8% greater than 3D-CRT and 14%-16% greater than ENI. Comparing the treatment techniques in this manner, we found only minor differences between 3D-CRT and IMRT, but clearly greater risks of pulmonary and esophageal toxicity with ENI. The mean lung V(20) was 36% with ENI vs. 23%-25% with the three other techniques, whereas the average mean lung dose was approximately 21.5 Gy (ENI) vs. 15.5 Gy (others). Similarly, the mean esophagus V(50) was doubled with ENI, to 34% rather than 15%-18%. To account for differences in heterogeneity, we also compared the techniques giving each plan a tumor control probability equivalent to that of the optimized 3D-CRT plan delivering 70 Gy. Using this method, IMRT and 3D-CRT offered similar results in node-negative cases (mean lung and esophageal normal-tissue complication probability [NTCP] of approximately 10% and 2%-7%, respectively), but ENI was distinctly worse (mean NTCPs of 29% and 20%). In node-positive cases, however, IMRT reduced the lung V(20) and mean dose by approximately 15% and lung NTCP by 30%, compared to 3D-CRT. Compared to ENI, the reductions were 50% and >100%. Again, for node-positive cases, especially where the gross tumor volume was close to the esophagus, IMRT reduced the mean esophagus V(50) by 40% (vs. 3D-CRT) to 145% (vs. ENI). The esophageal NTCP was at least doubled converting from IMRT to 3D-CRT and tripled converting from IMRT to ENI. Finally, the total number of fractions for each plan was increased or decreased until all outlined normal-tissue constraints were reached/satisfied. While meeting all constraints, IMRT or 3D-CRT increased the deliverable dose in node-negative patients by >200% over ENI. In node-positive patients, IMRT increased the deliverable dose 25%-30% over 3D-CRT and 130%-140% over ENI. The use of 3D-CRT without IMRT increased the deliverable RT dose >80% over ENI. Using a limited number of 3D-CRT beams decreased the lung V(20), mean dose, and NTCP in node-positive patients. CONCLUSION: The use of 3D-CRT, particul mean dose, and NTCP in node-positive patients. The use of 3D-CRT, particularly with only 3 to 4 beam angles, has the ability to reduce normal-tissue toxicity, but has limited potential for dose escalation beyond the current standard in node-positive patients. IMRT is of limited additional value (compared to 3D-CRT) in node-negative cases, but is beneficial in node-positive cases and in cases with target volumes close to the esophagus. When meeting all normal-tissue constraints in node-positive patients, IMRT can deliver RT doses 25%-30% greater than 3D-CRT and 130%-140% greater than ENI. Whereas the possibility of dose escalation is severely limited with ENI, the potential for pulmonary and esophageal toxicity is clearly increased.

Carcinoma, Non-Small-Cell Lung↗

PubMed2003

Initial clinical experience with moderate deep-inspiration breath hold using an active breathing control device in the treatment of patients with left-sided breast cancer using external beam radiation therapy.

INTRODUCTION: We present our initial clinical experience using moderate deep-inspiration breath hold (mDIBH) with an active breathing control (ABC) device to reduce heart dose in the treatment of patients with early-stage, left-sided breast cancer using external beam radiation therapy (EBRT) limited to the whole breast. METHODS AND MATERIALS: Between February and August 2002, 5 patients with Stages I/II left-sided breast cancer received EBRT limited to the whole breast using an ABC device. After standard virtual simulation, patients with >2% of the heart receiving >30 Gy in free breathing were selected. All patients underwent a training session with the ABC apparatus to determine their ability to comfortably maintain mDIBH at 75% of the maximum inspiration capacity. Three patients received 45 Gy to the whole breast in 25 fractions, and 2 patients received 50.4 Gy in 28 fractions. For each of the medial and lateral tangential beams, radiation was delivered during 2 or 3 breath hold durations that ranged from 18 to 26 s. "Step-and-shoot" intensity modulation was employed to achieve uniform dose distribution. Open beam segments were purposely delivered over 2 breath hold sessions and captured on electronic portal images to allow intra- and interfraction setup error analysis. All electronic portal images of the tangential beams were analyzed off-line using an in-house treatment verification tool to assess the anteroposterior, craniocaudal, and rotational uncertainties. Corrections were applied if necessary. RESULTS: A comparison of treatment plans performed on breath-hold and free-breathing CTs showed that ABC treatments achieved a mean absolute reduction of 3.6% in heart volume receiving 30 Gy (heart V(30)) and 1.5% in the heart normal tissue complication probability. A total of 134 ABC treatment sessions were performed in the 5 patients. The average number of breath holds required per beam direction was 2.5 (4-6 per treatment) with a median duration of 22 s per breath hold (range: 10-26 s). Patients tolerated mDIBH well. The median treatment time was 18.2 min (range: 13-32 min), which was progressively shortened with increasing experience. A total of 509 portal images were analyzed. Combining measurements for all patients, the interfraction setup errors (1 SD) in the lateral and craniocaudal directions and in rotation were 2.4 mm, 3.2 mm, and 1 degrees, respectively, for the medial beam and 2.3 mm, 3.1 mm, and 1 degrees, respectively, for the lateral beam. For all patients, the intrafraction setup errors were about 1 mm and always less than 2 mm (1 SD). CONCLUSION: Reduction in heart V(30) can be achieved in patients with left-sided breast cancer using mDIBH assisted with an ABC device. With increasing experience, ABC treatments were streamlined and could be performed within a 15-min treatment slot. Our results suggest that mDIBH using an ABC device may provide one of the most promising methods of improving the efficacy of EBRT in patients with left-sided breast cancer, particularly when wide tangential beams are employed. Breast cancer; Breath hold; Radiation therapy; Intensity modulated radiation therapy

Adult↗

PubMed2003

Accelerated partial breast irradiation using 3D conformal radiation therapy (3D-CRT).

PURPOSE: We present a novel three-dimensional conformal radiation therapy (3D-CRT) technique to treat the lumpectomy cavity, plus a 1.5-cm margin, in patients with early-stage breast cancer and study its clinical feasibility. METHODS AND MATERIALS: A 3D-CRT technique for partial-breast irradiation was developed using archived CT scans from 7 patients who underwent an active breathing control study. The clinical feasibility of this technique was then assessed in 9 patients who were prospectively enrolled on an Investigational Review Board-approved protocol of partial-breast irradiation. The prescribed dose was 34 Gy in 5 patients and 38.5 Gy in 4 patients, delivered in 10 fractions twice daily over 5 consecutive days. The impact of both breathing motion and patient setup uncertainty on clinical target volume (CTV) coverage was studied, and an appropriate CTV-to-PTV (planning target volume) margin was calculated. RESULTS: By adding a CTV-to-PTV "breathing-only" margin of 5 mm, 98%-100% of the CTV remained covered by the 95% isodose surface at the extremes of normal inhalation and normal exhalation. The "total" CTV-to-PTV margin employed to accommodate organ motion and setup error (10 mm) was found to be sufficient to accommodate the observed uncertainty in the delivery precision. Patient tolerance was excellent, and acute toxicity was minimal. No skin changes were noted during treatment, and at the initial 4-8-week follow-up visit, only mild localized hyperpigmentation and/or erythema was observed. No instances of symptomatic radiation pneumonitis have occurred. CONCLUSIONS: Accelerated partial-breast irradiation using 3D-CRT is technically feasible, and acute toxicity to date has been minimal. A CTV-to-PTV margin of 10 mm seems to provide coverage for most patients. However, more patients and additional studies will be needed to validate the accuracy of this margin, and longer follow-up will be needed to assess acute and chronic toxicity, tumor control, and cosmetic results.

Aged↗

PubMed2003

Significant reductions in heart and lung doses using deep inspiration breath hold with active breathing control and intensity-modulated radiation therapy for patients treated with locoregional breast irradiation.

PURPOSE: To evaluate the heart and lung sparing effects of moderate deep inspiration breath hold (mDIBH) achieved using an active breathing control (ABC) device, compared with free breathing (FB) during treatment with deep tangents fields (DT) for locoregional (LR) irradiation of breast cancer patients, including the internal mammary (IM) nodes (IMNs). To compare the DT-mDIBH technique to other standard techniques and to evaluate the dosimetric effect of intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Fifteen patients (9 left-sided and 6 right-sided lesions) with Stages 0-III breast cancer underwent standard FB and ABC computed tomographic (CT) scans in the treatment position. A dosimetric planning study was performed. In FB, the 9 left-sided patients were planned with a 5-field technique where electron fields covering the IM region were matched to shallow tangents using wedges (South West Oncology Group [SWOG] protocol S9927 technique A). This method was compared with a 3-field DT technique covering the breast and the IMNs (SWOG S9927 technique B). Compensation with IMRT was then compared with wedges for each technique. For the 15 total patients, dosimetric planning using DT with IMRT was then reoptimized on the mDIBH CT data set for comparison. Dose-volume histograms for the clinical target volume (CTV) (including the IMNs), planning target volume (PTV), ipsilateral and contralateral breast, and organs at risk (OAR) were analyzed. In addition, normal tissue complication probabilities (NTCP) for lung and heart, mean lung doses, and the number of monitor units (MUs) for a 1.8 Gy fraction were compared. RESULTS: For the 9 left-sided patients, the mean percentage of heart receiving more than 30 Gy (heart V30) was lower with the 5-field wedged technique than with the DT wedged technique (6.8% and 19.1%, respectively, p < 0.004). For the DT technique, the replacement of wedges with IMRT slightly diminished the mean heart V30 to 16.3% (p < 0.51). The introduction of mDIBH to the DT-IMRT technique reduced the heart V30 by 81% to a mean of 3.1% (p < 0.0004). Compared with 5-field IMRT, DT-IMRT with mDIBH reduced the heart V30 for 6 of the 9 patients, entirely avoiding heart irradiation in 2 of these 6 patients. For DT-IMRT, mDIBH reduced the mean lung dose and NTCP to levels obtained with the 5-field IMRT technique. For the 15 patients planned with DT-IMRT in FB, the use of mDIBH reduced the mean percentage of both lungs receiving more than 20 Gy from 20.4% to 15.2% (p < 0.00007). With DT-IMRT, more than 5% of the contralateral breast received more than 10 Gy for 6 of the 9 left-sided patients in FB, 3 of those 9 patients in mDIBH, and only 1 of those 9 patients planned with 5 fields. The mean % of the PTV receiving more than 55 Gy (110% of the prescribed dose) was 36.4% for 5-field wedges, 33.4% for 5-field IMRT, 28.7% for DT-wedges, 12.5% for DT-IMRT, and 18.4% for DT-IMRT mDIBH. The CTV remained covered by the 95% isodose in all the DT plans but one (99.1% of the volume covered). DT-wedges required more MUs than DT-IMRT (mean of 645 and 416, respectively, p < 0.00004). CONCLUSION: mDIBH significantly reduces heart and lung doses when DT are used for LR breast irradiation including the IMNs. Compared with shallow tangents matched with electrons, DT with mDIBH reduces the heart dose (in most patients) and results in comparable lung toxicity parameters, but may increase the dose to the contralateral breast. IMRT improves dose homogeneity, slightly reduces the dose to the heart, and diminishes the number of MUs required.

Breast Neoplasms↗

PubMed2003

Improved outcome at 10 years for serous-papillary/clear cell or high-risk endometrial cancer patients treated by adjuvant high-dose whole abdomino-pelvic irradiation.

PURPOSE: The aim of the study was to evaluate the 10-year treatment outcome of utilizing adjuvant high-dose whole abdominal irradiation (WAPI technique) with a pelvic/vaginal boost in patients with stage I-III endometrial carcinoma at high risk for intra-abdominopelvic recurrence, including serous-papillary and clear cell histologies. MATERIAL AND METHODS: In a prospective nonrandomized trial, 132 patients were treated with adjuvant WAPI between November 1981 and October 2001. Forty-three patients (32%) were 1998 FIGO stage I-II and 89 (68%) were stage III. Pathological features included the following: 66 (52%) with deep myometrial invasion, 50 (38%) with positive peritoneal cytology, 89 (67%) with high-grade lesions, 25 (19%) with positive pelvic/para-aortic lymph nodes, and 58 (45%) with serous-papillary or clear cell histology. RESULTS: The mean follow up was 6.4 years (range 0.6-16.1). For the entire group, the 5- and 10-year cause-specific survival (CSS) was 77 and 72%, whereas the disease-free survival (DFS) was 55 and 45%. When stratified by histology the 5- and 10-year CSS for adenocarcinoma was 75 and 70%, while serous-papillary/clear cell was 80 and 74% (P = 0.314). The 5- and 10-year DFS for adenocarcinoma was 59 and 49%, whereas serous-papillary/clear cell was 49 and 38% (P = 0.563). For surgical stages I-II, the 5-year CSS was 83% for adenocarcinoma and 89% for serous-papillary (P = 0.353). For stage III, it was 73 and 62% (P = 0.318), respectively. Forty-six patients (35%) relapsed. The first site of failure was the abdomen/pelvis in 27/46 (59%). When stratified by histologic variant, 34% of patients with adenocarcinoma and 41% with serous-papillary developed recurrent disease. In multivariate regression analysis only advancing age was of prognostic significance for CSS (P = 0.025) and DFS (P = 0.026). Chronic grade 3/4 GI toxicity was seen in 14%, and 2% of patients developed grade 3 renal toxicity. CONCLUSION: High-dose adjuvant WAPI is very effective treatment with excellent 10-year results for stage I-III endometrial carcinoma with risk factors for intra-abdominopelvic recurrence, including serous-papillary or clear cell histology. The low long-term complication rate with high CSS makes high-dose WAPI the treatment of choice for these patients with significant comorbidities.

Adenocarcinoma, Clear Cell↗

PubMed2002

Ten-year outcome including patterns of failure and toxicity for adjuvant whole abdominopelvic irradiation in high-risk and poor histologic feature patients with endometrial carcinoma.

PURPOSE: To evaluate the long-term results of treatment using adjuvant whole abdominal irradiation (WAPI) with a pelvic/vaginal boost in patients with Stage I-III endometrial carcinoma at high risk of intra-abdominopelvic recurrence, including clear cell (CC) and serous-papillary (SP) histologic features. METHODS AND MATERIALS: In a prospective nonrandomized trial, 119 patients were treated with adjuvant WAPI between November 1981 and April 2000. All patients were analyzed, including those who did not complete therapy. The mean age at diagnosis was 66 years (range 39-88). Thirty-eight patients (32%) had 1989 FIGO Stage I-II disease and 81 (68%) had Stage III. The pathologic features included the following: 64 (54%) with deep myometrial invasion, 48 (40%) with positive peritoneal cytologic findings, 69 (58%) with high-grade lesions, 21 (18%) with positive pelvic/para-aortic lymph nodes, and 44 (37%) with SP or CC histologic findings. RESULTS: The mean follow-up was 5.8 years (range 0.2-14.7). For the entire group, the 5- and 10-year cause-specific survival (CSS) rate was 75% and 69% and the disease-free survival (DFS) rate was 58% and 48%, respectively. When stratified by histologic features, the 5- and 10-year CSS rate for adenocarcinoma was 76% and 71%, and for serous papillary/CC subtypes, it was 74% and 63%, respectively (p = 0.917). The 5- and 10-year DFS rate for adenocarcinoma was 60% and 50% and was 54% and 37% serous papillary/CC subtypes, respectively (p = 0.498). For surgical Stage I-II, the 5-year CSS rate was 82% for adenocarcinoma and 87% for SP/CC features (p = 0.480). For Stage III, it was 75% and 57%, respectively (p = 0.129). Thirty-seven patients had a relapse, with the first site of failure the abdomen/pelvis in 14 (38%), lung in 8 (22%), extraabdominal lymph nodes in 7 (19%), vagina in 6 (16%), and other in 2 (5%). When stratified by histologic variant, 32% of patients with adenocarcinoma and 30% with the SP/CC subtype developed recurrent disease. Most failures for either histologic group occurred within the abdominopelvic region. However, one-third of the adenocarcinoma recurrences were in the lung. Multivariate regression analysis (age, surgical stage, grade, myometrial invasion, histologic type, lymph node status, and peritoneal cytology) demonstrated age (p = 0.019) and surgical stage (p = 0.036) to be of prognostic significance for CSS; age (p = 0.036) was the only significant prognostic factor for DFS. Grade 1-2 gastrointestinal and hematologic acute toxicities were common. Asymptomatic bibasilar scarring on chest X-ray and mild elevation of liver enzymes were seen in almost 50% of the patients. Even though chronic toxicities were less frequent, 12% developed Grade 3-4 gastrointestinal and 2% Grade 3 renal toxicities. CONCLUSION: Adjuvant WAPI is very effective treatment with excellent 10-year results for Stage I-III endometrial carcinoma with risk factors for intra-abdominopelvic recurrence, including SP or CC histologic variants, deep myometrial invasion, high grade, nodal involvement, and positive peritoneal cytology. The low long-term complication rate with high CSS rate makes WAPI the treatment of choice for these patients with significant comorbidities.

Actuarial Analysis↗

PubMed2002

Pathologic evidence of dose-response and dose-volume relationships for prostate cancer treated with combined external beam radiotherapy and high-dose-rate brachytherapy.

PURPOSE: The clinical significance of postradiotherapy (RT) prostate biopsy characteristics is not well understood relative to the known prognostic factors. We performed a detailed pathologic review of posttreatment biopsy specimens in an attempt to clarify their relationship with clinical outcome and radiation dose. METHODS AND MATERIALS: Between 1991 and 1998, 78 patients with locally advanced prostate cancer were prospectively treated with external beam RT in combination with high-dose-rate brachytherapy at William Beaumont Hospital and had post-RT biopsy material available for a complete pathologic review. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen level > or =10.0 ng/mL, Gleason score > or =7, or clinical Stage T2b-T3cN0M0. Pelvic external beam RT (46.0 Gy) was supplemented with three (1991-1995) or two (1995-1998) ultrasound-guided transperineal interstitial (192)Ir high-dose-rate implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Post-RT prostate biopsies were performed per protocol at a median interval of 1.5 years after RT. All pre- and post-RT biopsy specimen slides from each case were reviewed by a single pathologist (N.S.G.). The presence and amount of residual cancer, most common RT-effect score, and least amount RT-effect score were analyzed. The median follow-up was 5.7 years. Biochemical failure was defined as three consecutive prostate-specific antigen rises. RESULTS: Forty patients (51%) had residual cancer in the post-RT biopsies. The 7-year biochemical control rate was 79% for patients with negative biopsies vs. 62% for those with positive biopsies with marked RT damage vs. 33% for those with positive biopsies with no or minimal RT damage. A greater percentage of positive pre-RT biopsy cores (p = 0.01), lower total RT dose (p = 0.001), lower dose per implant (p = 0.001), and greater percentage of positive post-RT biopsy cores (p = 0.01) were each associated with biochemical failure (Cox regression, univariate analysis). For patients with <25% positive post-RT biopsy cores, the 7-year biochemical control rate was 81% vs. a 62% biochemical control rate for those with 25-49% positive cores and only 32% for those with > or =50% positive cores (p = 0.01). On Cox multiple regression analysis, only the percentage of positive pre-RT biopsy cores and RT dose remained significantly associated with biochemical failure. Of all the factors analyzed, only the pretreatment cancer volume and lower RT dose were significantly associated with residual cancer and/or residual cancer with no or minimal RT damage. A greater percentage of positive pre-RT biopsy cores was associated with both a positive post-RT biopsy (p = 0.08) and a greater percentage of positive post-RT biopsy cores (p = 0.04). A lower total RT dose was associated with both a positive post-RT biopsy (p = 0.08) and a greater percentage of positive post-RT biopsy cores (p = 0.02). For patients who received <80 Gy (equivalent in 2-Gy fractions), 73% had positive post-RT biopsies vs. a 56% biopsy positivity rate for those who received 84-90 Gy and only 39% for those who received > or =92 Gy (p = 0.07). CONCLUSION: Patients with positive post-RT biopsies are more likely to experience biochemical failure, especially when the RT damage is minimal. Patients who have a larger pretreatment tumor volume or receive a lower RT dose are more likely to demonstrate post-RT biopsy positivity and biochemical failure.

Aged↗